Fibrosis in Pathology of Heart and Kidney: From Deep RNA-Sequencing to Novel Molecular Targets.

Diseases of the heart and the kidney, including heart failure and chronic kidney disease, can dramatically impair life expectancy and the quality of life of patients. The heart and kidney form a functional axis; therefore, functional impairment of 1 organ will inevitably affect the function of the other. Fibrosis represents the common final pathway of diseases of both organs, regardless of the disease entity. Thus, inhibition of fibrosis represents a promising therapeutic approach to treat diseases of both organs and to resolve functional impairment. However, despite the growing knowledge in this field, the exact pathomechanisms that drive fibrosis remain elusive. RNA-sequencing approaches, particularly single-cell RNA-sequencing, have revolutionized the investigation of pathomechanisms at a molecular level and facilitated the discovery of disease-associated cell types and mechanisms. In this review, we give a brief overview over the evolution of RNA-sequencing techniques, summarize most recent insights into the pathogenesis of heart and kidney fibrosis, and discuss how transcriptomic data can be used, to identify new drug targets and to develop novel therapeutic strategies.

A stepped wedge cluster randomized trial of graphical surveillance of kidney function data to reduce late presentation for kidney replacement therapy.

Late presentation for kidney replacement therapy (KRT) is an important cause of avoidable morbidity and mortality. Here, we evaluated the effect of a complex intervention of graphical estimated glomerular filtration rate (eGFR) surveillance across 15% of the United Kingdom population on the rate of late presentation using data routinely collected by the United Kingdom Renal Registry. A stepped wedge cluster randomized trial was established across 19 sites with eGFR graphs generated from all routine blood tests (community and hospital) across the population served by each site. Graphs were reviewed by trained laboratory or clinical staff and high-risk graphs reported to family doctors. Due to delays outside the control of clinicians and researchers few laboratories activated the intervention in their randomly assigned time period, so the trial was converted to a quasi-experimental design. We studied 6,100 kidney failure events at 20 laboratories served by 17 main kidney units. A total of 63,981 graphs were sent out. After adjustment for calendar time there was no significant reduction in the rate of presentation during the intervention period. Therefore, implementation of eGFR graph surveillance did not reduce the rate of late presentation for KRT after adjustment for secular trends. Thus, graphical surveillance is an intervention aimed at reducing late presentation, but more evidence is required before adoption of this strategy can be recommended.

Metabolites Associated With Uremic Symptoms in Patients With CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

RATIONALE & OBJECTIVE: The toxins that contribute to uremic symptoms in patients with chronic kidney disease (CKD) are unknown. We sought to apply complementary statistical modeling approaches to data from untargeted plasma metabolomic profiling to identify solutes associated with uremic symptoms in patients with CKD. STUDY DESIGN: Cross-sectional. SETTING & PARTICIPANTS: 1,761 Chronic Renal Insufficiency Cohort (CRIC) participants with CKD not treated with dialysis. PREDICTORS: Measurement of 448 known plasma metabolites. OUTCOMES: The uremic symptoms of fatigue, anorexia, pruritus, nausea, paresthesia, and pain were assessed by single items on the Kidney Disease Quality of Life-36 instrument. ANALYTICAL APPROACH: Multivariable adjusted linear regression, least absolute shrinkage and selection operator linear regression, and random forest models were used to identify metabolites associated with symptom severity. After adjustment for multiple comparisons, metabolites selected in at least 2 of the 3 modeling approaches were deemed "overall significant." RESULTS: Participant mean estimated glomerular filtration rate was 43mL/min/1.73m2, with 44% self-identifying as female and 41% as non-Hispanic Black. The prevalence of uremic symptoms ranged from 22% to 55%. We identified 17 metabolites for which a higher level was associated with greater severity of at least one uremic symptom and 9 metabolites inversely associated with uremic symptom severity. Many of these metabolites exhibited at least a moderate correlation with estimated glomerular filtration rate (Pearson's r≥0.5), and some were also associated with the risk of developing kidney failure or death in multivariable adjusted Cox regression models. LIMITATIONS: Lack of a second independent cohort for external validation of our findings. CONCLUSIONS: Metabolomic profiling was used to identify multiple solutes associated with uremic symptoms in adults with CKD, but future validation and mechanistic studies are needed. PLAIN-LANGUAGE SUMMARY: Individuals living with chronic kidney disease (CKD) often experience symptoms related to CKD, traditionally called uremic symptoms. It is likely that CKD results in alterations in the levels of numerous circulating substances that, in turn, cause uremic symptoms; however, the identity of these solutes is not known. In this study, we used metabolomic profiling in patients with CKD to gain insights into the pathophysiology of uremic symptoms. We identified 26 metabolites whose levels were significantly associated with at least one of the symptoms of fatigue, anorexia, itchiness, nausea, paresthesia, and pain. The results of this study lay the groundwork for future research into the biological causes of symptoms in patients with CKD.

Prognostic Capability of Clinical SYNTAX Score in Patients with Complex Coronary Artery Disease and Chronic Renal Insufficiency Undergoing Percutaneous Coronary Intervention.

Background: The SYNTAX score (SS) is useful for predicting clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). The clinical SYNTAX score (CSS), developed by combining clinical parameters with the SS, enhances the risk model's ability to predict clinical outcomes. However, prior research has not yet evaluated the prognostic capacity of CSS in patients with complex coronary artery disease (CAD) and chronic renal insufficiency (CRI) who are undergoing PCI. We aimed to demonstrate the prognostic potential of CSS in assessing long-term adverse events in this high-risk patient cohort. Methods: A total of 962 patients with left main and/or three-vessel CAD and CRI were enrolled in the study spanning from January 2014 to September 2017. The CSS was calculated by multiplying the SS by the modified age, creatinine, and left ventricular ejection fraction (ACEF) score (age/ejection fraction + 1 for each 10 mL of creatinine clearance < 60 mL/min per 1.73 m 2 ). The patients were categorized into three groups based on their CSS values: low-CSS group (CSS < 18.0, n = 321), mid-CSS group (18.0 ≤ CSS < 28.3, n = 317), and high-CSS group (CSS ≥ 28.3, n = 324) as per the tertiles of CSS. The primary endpoints were all-cause mortality (ACM) and cardiac mortality (CM). The secondary endpoints included myocardial infarction (MI), unplanned revascularization, stroke, and major adverse cardiac and cerebrovascular events (MACCE). Results: At the median 3-year follow-up, the high-CSS group exhibited higher rates of ACM (19.4% vs. 6.6% vs. 3.6%, p < 0.001), CM (15.6% vs. 5.1% vs. 3.2%, p = 0.003), and MACCE (33.8% vs. 29.0% vs. 20.0%, p = 0.005) in comparison to the low and mid-CSS groups. Multivariable Cox regression analysis revealed that CSS was an independent predictor for all primary and secondary endpoints (p < 0 .05). Moreover, the C-statistics of CSS for ACM (0.666 vs. 0.597, p = 0.021) and CM (0.668 vs. 0.592, p = 0.039) were significantly higher than those of SS. Conclusions: The clinical SYNTAX score substantially enhanced the prediction of median 3-year ACM and CM in comparison with SS in complex CAD and CRI patients following PCI.

External validation of the SYNTAX score II 2020 in patients with chronic renal insufficiency.

BACKGROUND: The SYNTAX score Ⅱ 2020 (SSⅡ-2020) was created as a customized decision-making tool for individuals diagnosed with complex coronary artery disease (CAD). Nevertheless, there has been a scarcity of research investigating the long-term predictive significance of SSⅡ-2020 for patients with both CAD and chronic renal insufficiency (CRI) who undergo percutaneous coronary intervention (PCI). AIMS: We sought to showcase the prognostic capacity of SSII-2020 in evaluating long-term all-cause mortality (ACM) within this high-risk patient cohort. METHODS: A retrospective cohort comprising 1156 individuals diagnosed with CRI and exhibiting left main CAD, three-vessel CAD or both was included in this investigation. We categorized participants into three groups based on the optimal SSII-2020 threshold for predicting long-term ACM, determined using the X-tile software. RESULTS: At the median follow-up duration of 6.3 years, the ACM rates were determined to be 10% in the low, 17% in the moderate, and 28% in the high SSII-2020 groups (p < 0.001). Employing multivariate Cox regression analysis, it was observed that the high SSII-2020 group exhibited a 3.289-fold increased risk of ACM (95% confidence interval [CI]: 2.229-4.856, p < 0.001) compared with the low SSII-2020 group, whereas the high SSII-2020 group displayed a 1.757-fold (95% CI: 1.190-2.597, p = 0.005) in comparison to the median SSII-2020 groups. Compared with SSII, the SSII-2020 had an incremental value for predicting 7-year ACM (C-index: 0.662 vs. 0.534, p = 0.007; IDI: 0.016, p < 0.001). CONCLUSIONS: SSII-2020 enhances long-term ACM prediction, facilitates improved risk stratification, and improves clinical utility for PCI patients with complex CAD and CRI.

Long-term renal and cardiovascular risks of tacrolimus in patients with lupus nephritis.

BACKGROUND AND HYPOTHESIS: Despite continuous advancement, treatment of lupus nephritis (LN) remains challenging. Recent guidelines now include a regimen incorporating tacrolimus as a first-line treatment option. Even though tacrolimus is effective in combination with mycophenolate and corticosteroids, concerns remain regarding long-term use, given its association with increased cardiovascular risks including nephrotoxicity, hypertension, dyslipidemia and hyperglycemia in kidney transplant recipients. However, in LN, long-term evaluations and head-to-head comparisons are lacking and thus the safety profile remains ill-defined. We hypothesized that chronic toxicity also occurs in LN patients. Therefore, this study aimed to assess long-term cardiovascular and renal outcomes of tacrolimus in LN patients. METHODS: This observational cohort study examined adult LN patients treated with tacrolimus, assessing renal outcomes, hypertension, diabetes, dyslipidemia, cardiovascular events and the Framingham risk score. The results were compared to a control group of CNI-naïve LN patients. RESULTS: Of the 219 LN patients in this study, 43 (19.6%) had tacrolimus exposure. Over a median follow-up of 7.1 years, tacrolimus use was associated with significant kidney function decline (6.8 ml/min/1.73m2, versus 0.8 in the control group). The incidence of end-stage kidney disease was similar. Cardiovascular event incidence was equally low in both groups. The 10-year risk of coronary heart disease was lower in the tacrolimus group, primarily due to age differences. HbA1c levels were higher in the tacrolimus group (37.4 mmol/mol) than in controls (33.6 mmol/mol), although the incidence of diabetes was similar. There were no differences in the occurrence of hypertension or dyslipidemia. CONCLUSIONS: Our study demonstrated that tacrolimus exposure was associated with long-term kidney function loss in LN patients. Although cardiovascular risk factors and events were similar to patients never exposed to tacrolimus, there may be an increased risk of developing diabetes. Therefore, our study supports vigilance towards renal adverse effects in LN patients treated with tacrolimus.

[Management of cardiovascular diseases in patients with diabetes : ESC guidelines 2023]. / Management kardiovaskulärer Erkrankungen bei Patienten mit Diabetes : ESC-Leitlinie 2023.

Patients with diabetes mellitus have an increased risk for the development of cardiovascular diseases. The presence of both comorbidities has a major impact not only on the prognosis of the patients but is also decisive for the implementation of evidence-based treatment strategies for reduction of the cardiovascular risk. The new guidelines of the European Society of Cardiology (ESC) were published in 2023 and provide clear recommendations for the management of cardiovascular diseases in patients with diabetes. The most relevant aspects of these guidelines are summarized in the following overview article.

CO2 is the contrast media to choose in patients with initial Chronic Kidney Disease undergoing endovascular aneurysm repair to prevent further renal function deterioration.

OBJECTIVE: Even low quantities of iodine contrast media (ICM) could be responsible for exacerbation of a chronic kidney disease (CKD). Aim of this study was to determine whether it is more reasonable to perform endovascular aneurysm repair (EVAR) procedures in patients with initial CKD using CO2 rather than ICM to prevent further kidney deterioration. METHODS: A retrospective analysis was performed at our institution to identify patients with preoperative CKD at initial stage (class G3a-G3b according to KDOQI-KDIGO classification) who underwent either CO2-EVAR or ICM-EVAR. Primary endpoint was renal function evaluation; secondary endpoints were technical success, perioperative complications, hospital stay, and reinterventions and overall mortality at follow-up. RESULTS: Both CO2-EVAR and ICM-EVAR groups were composed of 21 patients. There were no differences in demographics, anatomy, and comorbidities, apart from worse ASA score in CO2-EVAR group (100% vs 57.1%, p = .001). Preoperative serum creatinine and glomerular filtration rates (GFR) were comparable (1.73 vs 1.6 mg/dl, p = .082 and 39.71 vs 43.04 mL/min/1.73 m2, p = .935). At follow-up (16.7 ± 18.1 months), CO2-EVAR was not associated with significant changes in creatinine and GFR, whereas ICM-EVAR determined a significant increase in creatinine (1.6 mg/dl vs 1.91 mg/dl, p = .04) and decrease in GFR values (43 vs 37.9 mL/min/1.73 m2, p = .04), determining the need for dialysis in one patient. CONCLUSIONS: ICM seems to be a determining factor in worsening renal function; therefore, an effort should be made to standardize the use of CO2 as the contrast medium of choice in patients with initial renal insufficiency undergoing EVAR.

Renal function, sex and age influence purines and pyrimidines in urine and could lead to diagnostic misinterpretation.

Glomerular filtration rate (GFR) is commonly used in clinical practice for the diagnosis and follow-up of chronic kidney disease. Screening for inborn errors of metabolism (IEM) is based on analysis of biomarkers in urine, reported by their ratio to urinary creatinine (crn). Impaired renal function may complicate the interpretation of several biomarkers used for screening of IEM. Our goal was to investigate the influence of kidney function, in terms of measured GFR (mGFR) on purines and pyrimidines in urine, in addition to the relationship to sex, age, pH and ketosis. Children (n = 96) with chronic kidney disease (CKD), in different CKD stages, were included. Urine samples were obtained prior to the injection of iohexol. Serum samples at 7 time-points were used to calculate mGFR based on iohexol plasma clearance. The association with sex, age, ketosis and pH was examined in samples of the laboratory production from 2015 to 2021 (n = 8192). Age was a highly significant covariate for all markers. GFR correlated positively to several purines and pyrimidines; the ratios hypoxanthine/crn, xanthine/crn and urate/crn (p = 2.0 × 10-14, < 3 × 10-15 and 7.2 × 10-4, respectively), and the ratios orotic acid/crn, uracil/crn, and carbamyl-ß-alanine/crn (p = 0.03, 1.4 × 10-6 and 0.003, respectively). The values of urate/crn, xanthine/crn, uracil/crn, and carbamyl-ß-alanine/crn were higher in females above 16 years of age. Ketosis and pH influenced some markers. In conclusion, decreased renal function interferes with the excretion of urinary purines and pyrimidines, and this could change decision limits substantially, e.g. result in false negative results in Lesch-Nyhan syndrome. SYNOPSIS: GFR influences purines and pyrimidines in urine. Clinical Trial Registration: ClinicalTrials.gov, Identifier NCT01092260, https://clinicaltrials.gov/ct2/show/NCT01092260?term=tondel&rank=2.

Chronic kidney disease of unknown aetiology: A comprehensive review of a global public health problem.

The term chronic kidney disease of unknown aetiology (CKDu) refers to chronic kidney disease (CKD) in the absence of diabetes, long-standing hypertension, glomerulonephritis, obstructive uropathy or other apparent causes. An increasing number of CKDu cases have been reported from Latin America, Sri Lanka, India and others over the last two decades. These regional nephropathies share the following common attributes: (a) they affect low-to-middle income countries with tropical climates, (b) involve predominantly rural agricultural communities, (c) male predilection, (d) absence of significant proteinuria and hypertension, and (e) chronic tubulointerstitial nephritis on kidney biopsy. The current body of literature suggests that CKDu may be caused by heat stress, agrochemicals, contaminated drinking water or heavy metals; however, considerable regional disparities in CKDu research make it difficult to establish a common causal link. In the absence of a definite aetiology, specific preventive and therapeutic interventions are lacking. Improvement of working conditions of farmers and labourers, provision of safe drinking water and changes in agricultural practices are some of the measures that have been implemented; however, there is lack of data to assess their impact on the incidence and progression of CKDu. There is a need for a concerted global effort to address the current knowledge gaps, and to develop effective and sustainable strategies to tackle this devastating disease.

Glucose Derivative Induced Vasculopathy in Children on Chronic Peritoneal Dialysis.

[Figure: see text].

The effect of micro-particle curcumin on chronic kidney disease progression: the MPAC-CKD randomized clinical trial.

BACKGROUND: Curcumin is a commonly used herbal supplement with anti-inflammatory and anti-fibrotic properties. Animal studies and small human trials suggest that curcumin reduces albuminuria in patients with chronic kidney disease (CKD). Micro-particle curcumin is a new, more bioavailable formulation of curcumin. METHODS: To determine whether micro-particle curcumin versus placebo slows the progression of albuminuric CKD we conducted a randomized, double-blind, placebo-controlled trial with 6-month follow-up. We included adults with albuminuria [a random urine albumin-to-creatinine ratio >30 mg/mmol (265 mg/g) or a 24-h urine collection with more than 300 mg of protein] and an estimated glomerular filtration rate (eGFR) between 15 and 60 mL/min/1.73 m2 within the 3 months before randomization. We randomly allocated participants 1:1 to receive micro-particle curcumin capsules (90 mg/day) or matching placebo for 6 months. After randomization, the co-primary outcomes were the changes in albuminuria and the eGFR. RESULTS: We enrolled 533 participants, but 4/265 participants in the curcumin group and 15/268 in the placebo group withdrew consent or became ineligible. The 6-month change in albuminuria did not differ significantly between the curcumin and placebo groups [geometric mean ratio 0.94, 97.5% confidence interval (CI) 0.82 to 1.08, P = .32]. Similarly, the 6-month change in eGFR did not differ between groups (mean between-group difference -0.22 mL/min/1.73 m2, 97.5% CI -1.38 to 0.95, P = .68). CONCLUSIONS: Ninety milligrams of micro-particle curcumin daily did not slow the progression of albuminuric CKD over 6 months. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02369549.

Physical exercise as a modulator of the purinergic system in the control of sarcopenia in individuals with chronic kidney disease on hemodialysis.

The word sarcopenia derives from the Greek terms "sarx" for meat and "penia" for loss, thus being used to define reductions in muscle mass, muscle strength, and lower physical performance that compromise, mainly, the elderly population. Its high negative impact on patients' quality of life encourages the production and publication of new studies that seek to find methods to prevent and reverse cases of loss of muscle mass and strength. Furthermore, the high prevalence of sarcopenia in patients with chronic kidney disease (CKD) is closely related to its pathophysiology, which consists of a state of increased protein catabolism and decreased muscle tissue synthesis. Also considering the inflammatory nature of CKD and sarcopenia, the purinergic system has been an important target of studies, which seek to relate it to the two previous conditions. This system achieves anti-inflammatory action by inhibiting, through adenosine, pro-inflammatory factors such as interleukin-12 (IL-12), tumor necrosis factor alpha (TNF-α), and nitric oxide (NO), as well as by releasing anti-inflammatory substances such as interleukin-10 (IL-10). Simultaneously, the purinergic system presents pro-inflammatory activity, signaled by adenosine triphosphate (ATP), which occurs through the activation of T cells and the release of pro-inflammatory factors such as those mentioned above. Therefore, the ability of this system to act on inflammatory processes can promote positive and negative changes in the clinical aspect of patients with CKD and/or sarcopenia. Furthermore, it appears that there is a correlation between the practice of repeated physical exercise with the clinical improvement and in the quality of life of these patients, presenting a decrease in the levels of C-reactive protein (CRP), NTPDase, and the pro-inflammatory cytokine IL-6, such as increases in IL-10 resulting from modulation of the purinergic system. In this way, the present article seeks to evaluate the effect of physical exercise as a modulator of the purinergic system in the control of sarcopenia in patients with CKD on hemodialysis, in order to trace a relationship that can bring benefits both for biological markers and for quality of life of these patients.

The Long-Term Survival Outcome in Older Patients with Different Pathological Types of Chronic Kidney Disease.

INTRODUCTION: Chronic kidney diseases (CKDs) are prevalent in older people, and renal pathological manifestations are important for diagnosis, treatment, and prognosis. However, the long-term survival outcome and risk factors for older CKD patients with different pathological types are not fully understood and need to be further investigated. METHODS: Medical data were recorded and all-cause mortality was followed up in patients who underwent renal biopsy diagnosed in Guangdong Provincial People's Hospital from 2005 to 2015. Kaplan-Meier analysis was used to identify the incidence of survival outcomes. Multivariate Cox regression models and nomograms were applied to analyze pathological types and other factors for overall survival outcomes. RESULTS: 368 cases were included and the median follow-up was 85 (46.5, 111) months. Overall mortality was 35.6%. The highest mortality was in the mesangioproliferative glomerulonephritis (MPGN) group (88.9%), followed by amyloidosis (AMY) group (84.6%), and the lowest mortality was in the minimal change disease (MCD) group (21.9%). Moreover, multivariate Cox regression model showed that survival times of MPGN {hazard ratio (HR) = 8.215 (95% confidence interval [CI]: 2.735-24.674), p < 0.001} and AMY (HR = 6.130 [95% CI: 2.219-16.94], p < 0.001) were significantly shorter than MCD. In addition, age, lower baseline estimated glomerular filtration rate (eGFR), history of chronic obstructive pulmonary disease (COPD) and cerebrovascular accidents (CVA)/transient ischemic attack (TIA), MPGN, and AMY were independent risk factors for the mortality of older patients with CKD. CONCLUSION: The long-term survival outcome of older CKD patients showed differences among different pathological types, and MPGN, AMY, age, baseline eGFR, CVA/TIA, and COPD were independent predictors for mortality.

Short-term safety and efficacy of escalating doses of atorvastatin for dyslipidemia in children with predialysis chronic kidney disease stage 2-5.

BACKGROUND: Dyslipidemia is a potentially modifiable risk factor in patients with chronic kidney disease (CKD). Information on the safety and efficacy of statins in pediatric CKD is limited. METHODS: Patients with CKD stage 2-5 and aged 5-18 years with low-density lipoprotein cholesterol (LDL-C) > 130 mg/dL and/or non-high-density lipoprotein cholesterol (non-HDL-C) > 145 mg/dL were enrolled from September 2019 to February 2021. All patients were administered atorvastatin 10 mg/day, which was escalated to 20 mg/day if LDL-C remained > 100 mg/dL and/or non-HDL-C > 120 mg/dL at 12 weeks. Proportion of patients achieving target lipid levels (LDL-C ≤ 100 mg/dL and non-HDL-C ≤ 120 mg/dL) and adverse events were assessed at 24 weeks. RESULTS: Of 31 patients enrolled, target lipid levels were achieved in 45.2% (95% CI 27.8-63.7%) at 24 weeks; 22 patients required dose escalation to 20 mg at 12 weeks. There was no difference in median lipid level reduction with 10 (n = 9) versus 20 mg/day (n = 22, P = 0.3). Higher baseline LDL-C (OR 1.06, 95% CI 1.00-1.11) and older age (OR 36.5, 95% CI 2.57-519.14) were independent predictors of failure to achieve target lipid levels with 10 mg/day atorvastatin. None had persistent rise in AST/ALT > 3 times upper normal limit (UNL) or CPK > 10 times UNL. No differences were noted in adverse events due to atorvastatin 10 or 20 mg/day. CONCLUSION: Atorvastatin (10-20 mg/day) administered for 24 weeks was safe and effectively reduced LDL-C and non-HDL-C in children with CKD stages 2-5. Patients with higher baseline LDL-C required higher doses to achieve the target. A higher resolution version of the Graphical abstract is available as Supplementary information.

Management of Adults with Newly Diagnosed Atrial Fibrillation with and without CKD.

BACKGROUND: Atrial fibrillation (AF) is highly prevalent in CKD and is associated with worse cardiovascular and kidney outcomes. Limited data exist on use of AF pharmacotherapies and AF-related procedures by CKD status. We examined a large "real-world" contemporary population with incident AF to study the association of CKD with management of AF. METHODS: We identified patients with newly diagnosed AF between 2010 and 2017 from two large, integrated health care delivery systems. eGFR (≥60, 45-59, 30-44, 15-29, <15 ml/min per 1.73 m2) was calculated from a minimum of two ambulatory serum creatinine measures separated by ≥90 days. AF medications and procedures were identified from electronic health records. We performed multivariable Fine-Gray subdistribution hazards regression to test the association of CKD severity with receipt of targeted AF therapies. RESULTS: Among 115,564 patients with incident AF, 34% had baseline CKD. In multivariable models, compared with those with eGFR >60 ml/min per 1.73 m2, patients with eGFR 30-44 (adjusted hazard ratio [aHR] 0.91; 95% CI, 0.99 to 0.93), 15-29 (aHR, 0.78; 95% CI, 0.75 to 0.82), and <15 ml/min per 1.73 m2 (aHR, 0.64; 95% CI, 0.58-0.70) had lower use of any AF therapy. Patients with eGFR 15-29 ml/min per 1.73 m2 had lower adjusted use of rate control agents (aHR, 0.61; 95% CI, 0.56 to 0.67), warfarin (aHR, 0.89; 95% CI, 0.84 to 0.94), and DOACs (aHR, 0.23; 95% CI, 0.19 to 0.27) compared with patients with eGFR >60 ml/min per 1.73 m2. These associations were even stronger for eGFR <15 ml/min per 1.73 m2. There was also a graded association between CKD severity and receipt of AF-related procedures (vs eGFR >60 ml/min per 1.73 m2): eGFR 30-44 ml/min per 1.73 (aHR, 0.78; 95% CI, 0.70 to 0.87), eGFR 15-29 ml/min per 1.73 m2 (aHR, 0.73; 95% CI, 0.61 to 0.88), and eGFR <15 ml/min per 1.73 m2 (aHR, 0.48; 95% CI, 0.31 to 0.74). CONCLUSIONS: In adults with newly diagnosed AF, CKD severity was associated with lower receipt of rate control agents, anticoagulation, and AF procedures. Additional data on efficacy and safety of AF therapies in CKD populations are needed to inform management strategies.

Association of Clonal Hematopoiesis of Indeterminate Potential with Worse Kidney Function and Anemia in Two Cohorts of Patients with Advanced Chronic Kidney Disease.

BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) is an inflammatory premalignant disorder resulting from acquired genetic mutations in hematopoietic stem cells. This condition is common in aging populations and associated with cardiovascular morbidity and overall mortality, but its role in CKD is unknown. METHODS: We performed targeted sequencing to detect CHIP mutations in two independent cohorts of 87 and 85 adults with an eGFR<60 ml/min per 1.73m2. We also assessed kidney function, hematologic, and mineral bone disease parameters cross-sectionally at baseline, and collected creatinine measurements over the following 5-year period. RESULTS: At baseline, CHIP was detected in 18 of 87 (21%) and 25 of 85 (29%) cohort participants. Participants with CHIP were at higher risk of kidney failure, as predicted by the Kidney Failure Risk Equation (KFRE), compared with those without CHIP. Individuals with CHIP manifested a 2.2-fold increased risk of a 50% decline in eGFR or ESKD over 5 years of follow-up (hazard ratio 2.2; 95% confidence interval, 1.2 to 3.8) in a Cox proportional hazard model adjusted for age, sex, and baseline eGFR. The addition of CHIP to 2-year and 5-year calibrated KFRE risk models improved ESKD predictions. Those with CHIP also had lower hemoglobin, higher ferritin, and higher red blood cell mean corpuscular volume versus those without CHIP. CONCLUSIONS: In this exploratory analysis of individuals with preexisting CKD, CHIP was associated with higher baseline KFRE scores, greater progression of CKD, and anemia. Further research is needed to define the nature of the relationship between CHIP and kidney disease progression.

Chronic kidney disease patients' views of readiness and ability to use mHealth apps.

BACKGROUND: The use of mobile health (mHealth) applications, which provide opportunities to improve health and lessen health inequalities, is increasing. Studies assessing the readiness and ability of patients in Malaysia with chronic kidney disease (CKD) to use mobile phone apps to manage their health are limited. AIMS: This study aimed to assess the readiness and ability to use mHealth apps among patients with CKD in north-east Peninsular Malaysia. METHODS: A cross-sectional study was undertaken, using a convenience sample of 100 CKD medical inpatients in a tertiary teaching hospital. A structured, self-administered questionnaire on readiness and ability to use mHealth apps was adopted. FINDINGS: Nearly one in five patients (18%) actively used health applications. More than three-quarters (77%) were aged >40 years and a similar proportion were ready to use mHealth apps (78%), and nearly half (46%) were confident about connecting their device to wifi. There was a correlation between ability and readiness to use mHealth apps (r=0.4; P<0.05). CONCLUSIONS: Fewer than half of participants had a good command of mHealth applications. Therefore, support on the use of these apps is needed, and healthcare managers need to consider this.

The value of preventing constipation in patients treated with peritoneal dialysis: An advanced practice nursing study / Intérêt de la prévention de la constipation des patients traités par la dialyse péritonéale : une recherche de pratique infirmière avancée

Introduction: In 1989, experts developed the Rome criteria classification coupled with the use of the Bristol scale, to objectify the condition of functional constipation. Background: Nowadays, little is documented in the literature about transit disorders in patients with End-Stage Chronic Renal Failure treated with peritoneal dialysis, even though this causes non-negligible complications on the patient's morbidityÌ, comfort and quality of life. Objective: The main objective of our study was to evaluate the prevalence of constipation in CKD patients. Material and method: We conducted a retrospective multicenter data-driven study. Results: 74 patient records were analyzed. We found a prevalence of constipation of 58% in patients with CKD. Discussion: Our results showed that the prevalence of constipation is frequent in patients with CKD. It leads to a significant discomfort for the patient, an additional cost in terms of care and technical procedures and a failure of the peritoneal dialysis technique. Conclusion: Thus, the prevention of constipation in CKD patients would be relevant to limit complications and ensure a better quality of life.

Introduction: En 1989, des experts ont mis au point la classification des critères de Rome couplée à l'utilisation de l'échelle de Bristol, afin d'objectiver l'état de constipation fonctionnelle. Contexte: Aujourd'hui, la littérature documente peu les troubles du transit des patients en Insuffisance rénale chronique terminale (IRCT) traités par la Dialyse péritonéale (DP), alors même que cela engendre des complications non négligeables sur la morbidité, le confort et la qualité de vie du patient. Objectif: L'objectif principal de notre étude était d'évaluer la prévalence de la constipation des patients en IRCT. Matériel et méthode: Nous avons réalisé une étude rétrospective multicentrique sur données. Résultats: 74 dossiers patients ont été analysés. Nous avons mis en évidence une prévalence de la constipation de 58 % chez des patients atteints d'une IRCT. Discussion: Nos résultats ont démontré que la prévalence de la constipation est fréquente chez les patients atteints d'une IRCT. Elle entraîne un inconfort notable chez le patient, un surcoût au niveau des soins et des actes techniques, et un échec de la technique de dialyse péritonéale. Conclusion: Ainsi, la prévention de la constipation des patients en IRCT serait pertinente pour limiter les complications et leur assurer une meilleure qualité de vie.

The value of preventing constipation in patients treated with peritoneal dialysis: an advanced practice nursing study / Intérêt de la prévention de la constipation des patients traités par la dialyse péritonéale : une recherche de pratique infirmière avancée

Introduction: In 1989, experts developed the Rome criteria classification coupled with the use of the Bristol scale, to objectify the condition of functional constipation.Background Nowadays, little is documented in the literature about transit disorders in patients with End-Stage Chronic Renal Failure treated with peritoneal dialysis, even though this causes non-negligible complications on the patient’s morbidity, comfort and quality of life. Objective: The main objective of our study was to evaluate the prevalence of constipation in CKD patients. Material and method: We conducted a retrospective multicenter data-driven study. Results: 74 patient records were analyzed. We found a prevalence of constipation of 58 % in patients with CKD. Discussion: Our results showed that the prevalence of constipation is frequent in patients with CKD. It leads to a significant discomfort for the patient, an additional cost in terms of care and technical procedures and a failure of the peritoneal dialysis technique. Conclusion: Thus, the prevention of constipation in CKD patients would be relevant to limit complications and ensure a better quality of life.

Introduction: En 1989, des experts ont mis au point la classification des critères de Rome couplée à l'utilisation de l'échelle de Bristol, afin d'objectiver l'état de constipation fonctionnelle. Contexte: Aujourd'hui, la littérature documente peu les troubles du transit des patients en Insuffisance rénale chronique terminale (IRCT) traités par la Dialyse péritonéale (DP), alors même que cela engendre des complications non négligeables sur la morbidité, le confort et la qualité de vie du patient. Objectif: L'objectif principal de notre étude était d'évaluer la prévalence de la constipation des patients en IRCT. Matériel et méthode: Nous avons réalisé une étude rétrospective multicentrique sur données. Résultats: 74 dossiers patients ont été analysés. Nous avons mis en évidence une prévalence de la constipation de 58 % chez des patients atteints d'une IRCT. Discussion: Nos résultats ont démontré que la prévalence de la constipation est fréquente chez les patients atteints d'une IRCT. Elle entraîne un inconfort notable chez le patient, un surcoût au niveau des soins et des actes techniques, et un échec de la technique de dialyse péritonéale. Conclusion: Ainsi, la prévention de la constipation des patients en IRCT serait pertinente pour limiter les complications et leur assurer une meilleure qualité de vie.